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Pharmacopsychiatry 2011; 44(05): 183-188
DOI: 10.1055/s-0031-1280814
Original Paper
Georg Thieme Verlag KG Stuttgart · New York

Antipsychotics and Venous Thromboembolism Risk: A Meta-Analysis

R. Zhang
1   Department of Respiratory Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
,
L. Dong
1   Department of Respiratory Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
,
F. Shao
1   Department of Respiratory Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
,
X. Tan
1   Department of Respiratory Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
,
K. Ying
1   Department of Respiratory Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
› Author Affiliations
Further Information

Publication History

received 17 January 2011
revised 20 May 2011

accepted 24 May 2011

Publication Date:
07 July 2011 (online)

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Abstract

Background

Antipsychotics have been inconclusively implicated in susceptibility to venous thromboembolism (VTE).

Objectives and Methods

The aim of this study was to investigate the association between antipsychotic drugs and VTE risk by a meta-analysis. PubMed and EmBASE databases were searched for publications through to 10 October 2010. Statistical analysis was performed using Revman 4.2 and Stata 10.0 software.

Results

7 case-control studies involving 31 095 cases and 143 472 controls were analyzed. The results indicate that antipsychotic exposure confers a 139% increased risk of VTE (odds ratio [OR]=2.39, 95% confidence interval [CI]:1.71–3.35). Pooled estimates by drug type showed that use of low-potency antipsychotics (OR=2.91, 95% CI 1.80–4.71) is the most important risk factor for VTE, followed by atypical (OR=2.20, 95% CI 1.22–3.96), conventional (OR=1.72, 95% CI 1.31–2.24) and high-potency drugs (OR=1.58, 95% CI 1.50–1.67).

Conclusions

This meta-analysis suggests that antipsychotics are a risk factor for VTE. Additional studies in large cohorts are required to validate our findings. Future analyses should study potential effect modifications by different doses and durations of antipsychotic exposure in different populations.

Key words

antipsychotics - venous thromboembolism - risk factor - meta-analysis
 

  • References

  • 1 Zamagni E, Brioli A, Tacchetti P et al. Multiple myeloma, venous thromboembolism, and treatment-related risk of thrombosis. Semin Thromb Hemost 2011; 37: 209-219
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 O’Connor DJ, Scher LA, Gargiulo 3rd NJ et al. Incidence and characteristics of venous thromboembolic disease during pregnancy and the postnatal period: a contemporary series. Ann Vasc Surg 2011; 25: 9-14
    CrossrefPubMedGoogle Scholar
  • 3 Baron JA, Gridley G, Weiderpass E et al. Venous thromboembolism and cancer. Lancet 1998; 351: 1077-1080
    CrossrefPubMedGoogle Scholar
  • 4 Liperoti R, Pedone C, Lapane KL et al. Venous thromboembolism among elderly patients treated with atypical and conventional antipsychotic agents. Arch Intern Med 2005; 165: 2677-2682
    CrossrefPubMedGoogle Scholar
  • 5 Wakefield TW, Myers DD, Henke PK. Role of selectins and fibrinolysis in VTE. Thromb Res 2009; 123 (Suppl. 04) S35-S40
    PubMedGoogle Scholar
  • 6 Heit JA, Silverstein MD, Mohr DN et al. Predictors of survival after deep vein thrombosis and pulmonary embolism: a population-based, cohort study. Arch Intern Med 1999; 159: 445-453
    CrossrefPubMedGoogle Scholar
  • 7 Mohr DN, Silverstein MD, Heit JA et al. The venous stasis syndrome after deep venous thrombosis or pulmonary embolism: a population-based study. Mayo Clinic Proceed 2000; 75: 1249-1256
    PubMedGoogle Scholar
  • 8 Pineo GF, Hull RD. Economic and practical aspects of thromboprophylaxis with unfractionated and low-molecular-weight heparins in hospitalized medical patients. Clin Appl Thromb Hemost 2009; 15: 489-500
    CrossrefPubMedGoogle Scholar
  • 9 Spyropoulos AC. Risk assessment of venous thromboembolism in hospitalized medical patients. Curr Opin Pulm Med 2010; 16: 419-425
    CrossrefPubMedGoogle Scholar
  • 10 Goldhaber SZ. Risk factors for venous thromboembolism. J Am Coll Cardiol 2010; 56: 1-7
    CrossrefPubMedGoogle Scholar
  • 11 Rothberg MB, Lahti M, Pekow PS. Venous thromboembolism prophylaxis among medical patients at US hospitals. J Gen Intern Med 2011; 25: 489-494
    PubMedGoogle Scholar
  • 12 Jonsson AK, Horvath-Puho E, Hagg S et al. Antipsychotics and risk of venous thromboembolism: A population-based case-control study. Clin Epidemiol 2009; 1: 19-26
    PubMedGoogle Scholar
  • 13 Lacut K, Le Gal G, Couturaud F et al. Association between antipsychotic drugs, antidepressant drugs and venous thromboembolism: results from the EDITH case-control study. Fundam Clin Pharmacol 2007; 21: 643-650
    CrossrefPubMedGoogle Scholar
  • 14 Kleijer BC, Heerdink ER, Egberts TC et al. Antipsychotic drug use and the risk of venous thromboembolism in elderly patients. J Clinical Psychopharmacol 2010; 30: 526-530
    PubMedGoogle Scholar
  • 15 Parker C, Coupland C, Hippisley-Cox J. Antipsychotic drugs and risk of venous thromboembolism: nested case-control study. BMJ 2011; 341: c4245
    PubMedGoogle Scholar
  • 16 Zornberg GL, Jick H. Antipsychotic drug use and risk of first-time idiopathic venous thromboembolism: a case-control study. Lancet 2000; 356: 1219-1223
    CrossrefPubMedGoogle Scholar
  • 17 Jonsson AK, Brudin L, Ahlner J et al. Antipsychotics associated with pulmonary embolism in a Swedish medicolegal autopsy series. Int Clin Psychopharmacol 2008; 23: 263-268
    CrossrefPubMedGoogle Scholar
  • 18 Parkin L, Skegg DC, Herbison GP et al. Psychotropic drugs and fatal pulmonary embolism. Pharmacoepidemiol Drug Saf 2003; 12: 647-652
    CrossrefPubMedGoogle Scholar
  • 19 Walker AM, Lanza LL, Arellano F et al. Mortality in current and former users of clozapine. Epidemiology (Cambridge, Mass) 1997; 8: 671-677
    CrossrefPubMedGoogle Scholar
  • 20 Hagg S, Bate A, Stahl M et al. Associations between venous thromboembolism and antipsychotics. A study of the WHO database of adverse drug reactions. Drug Saf 2008; 31: 685-694
    CrossrefPubMedGoogle Scholar
  • 21 Hamanaka S, Kamijo Y, Nagai T et al. Massive pulmonary thromboembolism demonstrated at necropsy in Japanese psychiatric patients treated with neuroleptics including atypical antipsychotics. Circ J 2004; 68: 850-852
    CrossrefPubMedGoogle Scholar
  • 22 Ray JG, Mamdani MM, Yeo EL. Antipsychotic and antidepressant drug use in the elderly and the risk of venous thromboembolism. Thromb Haemost 2002; 88: 205-209
    PubMedGoogle Scholar
  • 23 Neuroleptics: increased rate of venous thromboembolic events. Prescrire international 2006; 15: 224
    PubMedGoogle Scholar
  • 24 Hagg S, Spigset O. Antipsychotic-induced venous thromboembolism: a review of the evidence. CNS drugs 2002; 16: 765-776
    CrossrefPubMedGoogle Scholar
  • 25 Wallaschofski H, Eigenthaler M, Kiefer M et al. Hyperprolactinemia in patients on antipsychotic drugs causes ADP-stimulated platelet activation that might explain the increased risk for venous thromboembolism: pilot study. J Clin Psychopharmacol 2003; 23: 479-483
    CrossrefPubMedGoogle Scholar
  • 26 Axelsson S, Hagg S, Eriksson AC et al. In vitro effects of antipsychotics on human platelet adhesion and aggregation and plasma coagulation. Clin Exper Pharmacol Physiol 2007; 34: 775-780
    CrossrefPubMedGoogle Scholar
  • 27 Rosendaal FR. Venous thrombosis: the role of genes, environment, and behavior. The Education Program of the American Society of Hematology. American Society of Hematology. Hematology 2005; 1-12
    PubMedGoogle Scholar
  • 28 Owens DG. Adverse effects of antipsychotic agents. Do newer agents offer advantages?. Drugs 1996; 51: 895-930
    CrossrefPubMedGoogle Scholar